Ch 20: Thyroid Gland

What are the products of the follicular cells of the thyroid?

• T3 (tri-iodothyronine)

• T4 (tetra-iodothyronine, thyroxine)

What is the role of the colloid in the thyroid gland?

Colloid contains thyroglobulin, a protein that binds and stores follicular cell secretions.

What is the function of C-cells in the thyroid gland?

These cells are responsible for the synthesis, storage, and secretion of a peptide hormone: calcitonin

What is the primary form of thyroid hormone released into the blood?

T4 (thyroxine)

Which form of thyroid hormone is more active?

tri-iodothyronine (T3)

What do peripheral tissues do to T4?

Peripheral tissues contain deiodinase enzymes to convert T4 to T3.

Where are the receptors for thyroid hormone? Why?

Thyroid Hormone receptors are in the nucleus of a target cell. Thyroid hormones are lipid soluble, so they can pass through the cell membrane.

What cotransporter is responsible for the movement of iodide into follicular cells?

A Sodium-Iodide co-transporter protein

What effects does TSH have on thyroid cells?

• stimulates follicular cells via GPCR cAMP messaging

• increases activity of NA/I cotransporter

• Stimulates endocytosis of thyroglobulin

• Stimulates proteolysis of TG to liberate T3 and T4

What are the 7 steps of TH synthesis?

• Iodide is trapped in the follicular cell via Na/I cotransporter

• Iodide enters the lumen, and is oxidized to iodine via thyroid peroxidase

• thyroglobulin is iodinated 

• iodinated thyroglobulin is conjugated to form T4 and T3 linked to thyroglobulin

• Iodinated thyroglobulin is endocytosed into follicular cells 

• the iodinated thyroglobulin is proteolyzed, freeing the T4 and T3 in the vesicle

• T4 and T3 are secreted into circulation. 

What transport protein is the majority of T4 bound to?

T4 is primarily bound to thyroxine-binding globulin and Transthyretin

What protein is T3 mostly bound to?

T3 is mostly bound to albumin (53%) but is also bound to Thyroxine-Binding Globulin (TBG)

What happens to T4/T3 upon entering the cell?

T3 can bind to TR receptors in the nucleus.

T4 can bind to TR receptors as well, but is less likely to do so. T4 may undergo deiodination and become T3 within the cytoplasm.  

What effect does thyroid hormone action have on a cell?

• increased Na-K pump production

• Increase in gluconeogenic enzymes

• Increased respiratory enzymes

• Increased production in myosin heavy chain

• increase in beta-adrenergic receptors (increased excitability)

What effect does thyroid hormone have on the heart?

• chronotropic and ionotropic

  • increased number of beta-adrenergic receptors

  • enhanced responses to circulating catecholamines

  • increased proportion of a-myosin heavy chain (greater ATPase activity, greater contractile rate)

What effect does thyroid hormone have on adipose tissue?

Catabolic

• stimulated lipolysis (freeing of FFA into blood)

What effect does thyroid hormone have on muscle tissue?

Catabolic

• increased protein breakdown

What effect does thyroid hormone have on bone tissue?

Developmental

• promotes normal growth and skeletal development

What effect does thyroid hormone have on the nervous system?

Developmental

• promotes normal brain development

What effect does thyroid hormone have on the digestive system?

Metabolic

• increased rate of carbohydrate absorption

What effect does thyroid hormone have on lipoproteins?

Metabolic

• increased formation of LDL receptors

What are the general effects of thyroid hormone?

Calorigenic in nature

• increase oxygen consumption by metabolically active tissues (except tests, uterus, lymph nodes, spleen, and AP gland)

• Increased metabolic rate

What is the most important regulator of TSH release?

Free T4 hormone detected by the AP gland will inhibit TSH release

What are some generic symptoms of hypothyroidism?

• weight gain

• sluggishness

• brain fog

What is myxedema?

a condition characterized by changes to the skin as a result of decreased basal cells (resulting from decreased skin proliferation)

What are some characteristics of hyperthyroidism?

• nervousness

• weight loss

• hyperphagia

• heat intolerance

• increased pulse

Symptoms stem from overactive metabolism an cellular activity. 

What is the most common cause of hyperthyroidism?

graves disease

What is graves disease?

• accounts for 60-80% of all cases of hyperthyroidism

• Autoimmune disease, more common in women, antibodies of TSH receptor stimulate the receptor.

• Elevated T4 and T3 secretion and enlargement of thyroid

Results in LOW levels of TSH due to negative feedback, TSH antibodies responsible for stimulation.

What is an ocular symptom of graves disease?

exophthalmos

• swelling of the tissues in the orbitals, results in protrusion of the eyeballs. 

What is Hashimoto Thyroiditis?

• Autoimmune antibodies and infiltrating cytotoxic T cells destroy the thyroid gland

• results in hypothyroidism

What is characteristic of early stage hasimoto thyroiditis?

inflammation of the gland resulting in excess thyroid hormone secretion and thyrotoxicosis.

presents similar to grave’s disease.